Browsing by Author "Hollander, Judd E"

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    Analytical performance evaluation of the Elecsys® Troponin T Gen 5 STAT assay.
    (Clinica chimica acta; international journal of clinical chemistry, 2019-08) Fitzgerald, Robert L; Hollander, Judd E; Peacock, W Frank; Limkakeng, Alexander T; Breitenbeck, Nancy; Blechschmidt, Kareen; Laimighofer, Michael; deFilippi, Christopher
    BACKGROUND:We report the analytical performance of the Elecsys® Troponin T Gen 5 STAT (TnT Gen 5 STAT; Roche Diagnostics) assay. METHODS:Measuring limits/ranges were determined in lithium-heparin plasma samples per Clinical and Laboratory Standards Institute (CLSI) EP17-A2. Precision was evaluated per CLSI EP05-A2 using lithium-heparin plasma/quality control samples on cobas e 411/cobas e 601 analyzers; two duplicated runs per day for 21 days (n = 84). Cross-reactivity with other troponin forms and interference from endogenous substances/drugs was tested; recovery criterion for no cross-reactivity was within ±10%. RESULTS:Coefficients of variation (CV) for repeatability/intermediate precision were 0.7-5.6%/1.4-10.3% (cobas e 411; mean cardiac troponin T [cTnT]: 7.3-9341 ng/L) and 0.7-3.0%/1.5-6.4% (cobas e 601; mean cTnT: 7.4-9455 ng/L). There was no cross-reactivity with skeletal muscle troponin T (≤ 10,000 ng/L), skeletal muscle troponin I (≤ 100,000 ng/L), cardiac troponin I (≤ 10,000 ng/L), or human troponin C (≤ 80,000 ng/L). No interference was observed with biotin (≤ 20 ng/mL) or 34 drugs. CONCLUSION:The TnT Gen 5 STAT assay demonstrated a CV of <10% at the 99th percentile upper reference limit, meeting precision requirements (Fourth Universal Definition of Myocardial Infarction) for high-sensitivity troponin assays.
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    Efficacy of High-Sensitivity Troponin T in Identifying Very-Low-Risk Patients With Possible Acute Coronary Syndrome.
    (JAMA cardiology, 2018-02) Peacock, W Frank; Baumann, Brigette M; Bruton, Deborah; Davis, Thomas E; Handy, Beverly; Jones, Christopher W; Hollander, Judd E; Limkakeng, Alexander T; Mehrotra, Abhi; Than, Martin; Ziegler, Andre; Dinkel, Carina
    Importance:Physicians need information on how to use the first available high-sensitivity troponin (hsTnT) assay in the United States to identify patients at very low risk for 30-day adverse cardiac events (ACE). Objective:To determine whether a negative hsTnT assay at 0 and 3 hours following emergency department presentation could identify patients at less than 1% risk of a 30-day ACE. Design, Setting, and Participants:A prospective, observational study at 15 emergency departments in the United States between 2011 and 2015 that included individuals 21 years and older, presenting to the emergency department with suspected acute coronary syndrome. Of 1690 eligible individuals, 15 (no cardiac troponin T measurement) and 320 (missing a 0-hour or 3-hour sample) were excluded from the analyses. Exposures:Serial hsTnT measurements (fifth-generation Roche Elecsys hsTnT assay). Main Outcomes and Measures:Serial blood samples from each patient were collected after emergency department presentation (once identified as a potential patient with acute coronary syndrome) and 3 hours, 6 to 9 hours, and 12 to 24 hours later. Adverse cardiac events were defined as myocardial infarction, urgent revascularization, or death. The upper reference level for the hsTnT assay, defined as the 99th percentile, was established as 19 ng/L in a separate healthy US cohort. Patients were considered ruled out for acute myocardial infarction if their hsTnT level at 0 hours and 3 hours was less than the upper reference level. Gold standard diagnoses were determined by a clinical end point committee. Evaluation of assay clinical performance for acute myocardial infarction rule-out was prespecified; the hypothesis regarding 30-day ACE was formulated after data collection. Results:In 1301 healthy volunteers (50.4% women; median age, 48 years), the upper reference level was 19 ng/L. In 1600 patients with suspected acute coronary syndrome (48.4% women; median age, 55 years), a single hsTnTlevel less than 6 ng/L at baseline had a negative predictive value for AMI of 99.4%. In 974 patients (77.1%) with both 0-hour and 3-hour hsTnT levels of 19 ng/L or less, the negative predictive value for 30-day ACE was 99.3% (95% CI, 99.1-99.6). Using sex-specific cutpoints, C statistics for women (0.952) and men (0.962) were similar for acute myocardial infarction. Conclusions and Relevance:A single hsTnT level less than 6 ng/L was associated with a markedly decreased risk of AMI, while serial levels at 19 ng/L or less identified patients at less than 1% risk of 30-day ACE.
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    Emergency physician high pretest probability for acute coronary syndrome correlates with adverse cardiovascular outcomes.
    (Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2009-08) Chandra, Abhinav; Lindsell, Christopher J; Limkakeng, Alexander; Diercks, Deborah B; Hoekstra, James W; Hollander, Judd E; Kirk, J Douglas; Peacock, W Frank; Gibler, W Brian; Pollack, Charles V; EMCREG i*trACS Investigators
    OBJECTIVES: The value of unstructured physician estimate of risk for disease processes, other than acute coronary syndrome (ACS), has been demonstrated. The authors sought to evaluate the predictive value of unstructured physician estimate of risk for ACS in emergency department (ED) patients without obvious initial evidence of a cardiac event. METHODS: This was a post hoc secondary analysis of the Internet Tracking Registry for Acute Coronary Syndromes (i*trACS), a prospectively collected multicenter data registry of patients over the age of 18 years presenting to the ED with symptoms of ACS between 1999 and 2001. In this registry, following patient history, physical exam, and electrocardiogram (ECG), the unstructured treating physician estimate of risk was recorded. A 30-day follow-up and a medical record review were used to determine rates of adverse cardiac events, death, myocardial infarction (MI), or revascularization procedure. The analysis included all patients with nondiagnostic ECG changes, normal initial biomarkers, and a non-MI initial impression from the registry and excluded those without complete data or who were lost to follow-up. Data were stratified by unstructured physician risk estimate: noncardiac, low risk, high risk, or unstable angina. RESULTS: Of 15,608 unique patients in the registry, 10,145 met inclusion/exclusion criteria. Patients were defined as having unstable angina in 6.0% of cases; high risk, 23.5% of cases; low risk, 44.2%; and noncardiac, 26.3% of cases. Adverse cardiac event rates had an inverse relationship, decreasing from 22.0% (95% confidence interval [CI] = 18.8% to 25.6%) for unstable angina, 10.2% (95% CI = 9.0% to 11.5%) for those stratified as high risk, 2.2% (95% CI = 1.8% to 2.6%) for low risk, and to 1.8% (95% CI = 1.4% to 2.4%) for noncardiac. The relative risk (RR) of an adverse cardiac event for those with an initial label of unstable angina compared to those with a low-risk designation was 10.2 (95% CI = 8.0 to 13.0). The RR of an event for those with a high-risk initial impression compared to those with a low-risk initial impression was 4.7 (95% CI = 3.8 to 5.9). The risk of an event among those with a low-risk initial impression was the same as for those with a noncardiac initial impression (RR = 0.83, 95% CI = 0.6 to 1.2). CONCLUSIONS: In ED patients without obvious initial evidence of a cardiac event, unstructured emergency physician (EP) estimate of risk correlates with adverse cardiac outcomes.
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    International, multicenter evaluation of a new D-dimer assay for the exclusion of venous thromboembolism using standard and age-adjusted cut-offs.
    (Thrombosis research, 2018-04-05) Parry, Blair Alden; Chang, Anna Marie; Schellong, Sebastian M; House, Stacey L; Fermann, Gregory J; Deadmon, Erin K; Giordano, Nicholas J; Chang, Yuchiao; Cohen, Jason; Robak, Nancy; Singer, Adam J; Mulrow, Mary; Reibling, Ellen T; Francis, Samuel; Griffin, S Michelle; Prochaska, Jürgen H; Davis, Barbara; McNelis, Patricia; Delgado, Joao; Kümpers, Philipp; Werner, Nikos; Gentile, Nina T; Zeserson, Eli; Wild, Philipp S; Limkakeng, Alexander T; Walters, Elizabeth Lea; LoVecchio, Frank; Theodoro, Daniel; Hollander, Judd E; Kabrhel, Christopher
    We sought to determine the test characteristics of an automated INNOVANCE D-dimer assay for the exclusion of pulmonary embolism (PE) and deep venous thrombosis (DVT) in emergency department (ED) patients using standard and age-adjusted cut-offs.Cross-sectional, international, multicenter study of consecutive patients with suspected DVT or PE in 24 centers (18 USA, 6 Europe). Evaluated patients had low or intermediate Wells PE or DVT scores. For the standard cut-off, a D-dimer result <500 ng/ml was negative. For the age adjusted cut-off, we used the formula: Age (years) ∗ 10. The diagnostic standard was imaging demonstrating PE or DVT within 3 months. We calculated test characteristics using standard methods. We also explored modifications of the age adjustment multiplier.We included 3837 patients and excluded 251. The mean age of patients evaluated for PE (n = 1834) was 48 ± 16 years, with 676 (37%) male, and 1081 (59%) white. The mean age of evaluated for DVT (n = 1752) was 53 ± 16 years, with 710 (41%) male, and 1172 (67%) white. D-dimer test characteristics for PE were: sensitivity 98.0%, specificity 55.4%, negative predictive value (NPV) 99.8%, positive predictive value (PPV) 11.4%, and for DVT were: sensitivity 92.0%, specificity 44.8%, NPV 98.8%, PPV 10.3%. Age adjustment increased specificity (59.6% [PE], 51.1% [DVT]), but increasing the age-adjustment multiplier decreased sensitivity without increasing specificity.INNOVANCE D-dimer is highly sensitive and can exclude PE and DVT in ED patients with low- and intermediate- pre-test probability. Age-adjustment increases specificity, without increasing false negatives.
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    The 99th percentile upper reference limit for the 5th generation cardiac troponin T assay in the United States.
    (Clinica chimica acta; international journal of clinical chemistry, 2020-05) Fitzgerald, Robert L; Hollander, Judd E; Peacock, W Frank; Limkakeng, Alexander T; Breitenbeck, Nancy; Rivers, E Joy; Ziegler, André; Laimighofer, Michael; deFilippi, Christopher
    BACKGROUND:Determining diagnostic thresholds for cardiac troponin assays is key to interpreting their clinical performance. We describe the calculation of 99th percentile upper reference limits (URLs) for the Elecsys® Troponin T Gen 5 (TnT Gen 5) assay. METHODS:Plasma and serum samples from healthy US participants were prospectively evaluated using TnT Gen 5 Short Turn Around Time and 18-min assays on cobas e 411 and cobas e 601 analyzers (Roche Diagnostics); with, up to 8 TnT Gen 5 results per participant. RESULTS:A total of 10,402 TnT Gen 5 results from 1301 participants were included (50.4% female). Across 9 calculation methods, overall 99th percentile URL was 19.2 ng/l (females, 13.5-13.6 ng/l; males, 21.4-22.2 ng/l). Across different sample/assay/analyzer combinations, overall 99th percentile URLs ranged from 18.4-20.2 ng/l. Median TnT Gen 5 results increased with age, were higher in males, and ranged from 3.0-3.7 ng/l across races/ethnicities and from 3.0-3.6 ng/l across body mass index (BMI) classes. Applying additional exclusion criteria (N-terminal pro-brain natriuretic peptide, BMI and estimated glomerular filtration rate) resulted in lower 99th percentile URLs (overall, 16.9 ng/l; females, 11.8 ng/l; males, 18.5 ng/l). CONCLUSION:Our findings facilitate the interpretation of TnT Gen 5 results in US clinical practice.
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    Using Sex-specific Cutoffs for High-sensitivity Cardiac Troponin T to Diagnose Acute Myocardial Infarction.
    (Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2020-07-29) Peacock, W Frank; Baumann, Brigitte M; Rivers, E Joy; Davis, Thomas E; Handy, Beverly; Jones, Christopher W; Hollander, Judd E; Limkakeng, Alexander T; Mehrotra, Abhi; Than, Martin; Cullen, Louise; Ziegler, André; Dinkel-Keuthage, Carina
    High-sensitivity cardiac troponin (hs-cTn) assays facilitate early decision-making in acute myocardial infarction (AMI).1 The accuracy of these assays now allow sex-specific differences in levels to be detected within healthy populations. It is thought that differences in plasma levels of cardiac troponin (cTn) are due to sex-specific variations in body composition and cardiac physiology,2 and that estrogen may also play a part.3 However, the clinical relevance of this remains unclear.4 Women presenting with suspected acute coronary syndrome (ACS) are less frequently diagnosed, have poorer outcomes,5 and are more likely to have atypical symptoms than men.6 The requirement for sex-specific cutoffs may vary depending on the troponin assay, intended use, AMI type, and clinical performance estimate being assessed. Previously proposed sex-specific hs-cTnT assay cutoffs (females, 14 ng/L; males, 22 ng/L) did not alter sensitivity for AMI versus the overall cutoff (19 ng/L), but resulted in slightly lower specificity for AMI in females and higher specificity in males.4 However, it is uncertain whether sex-specific cutoffs improve hs-cTnT assay diagnostic performance.